Anthroposophic Medicinal Products: A Literature Review of Features, Similarities and Differences to Conventional Medicinal Products, Scientific and Regulatory Assessment.

Background: Regulatory assessment of anthroposophic medicinal products (AMPs) can be challenging due to their specific features. Objective: The aim of this paper is therefore to provide adequate scientific information on AMPs for regulatory purposes. Methods: A literature review was executed with database searches in PubMed, Cinahl, Merkurstab, Anthromedics, and https://iaap-pharma.org/. Search terms were: anthroposophic medicinal products, anthroposophic medicines, anthroposophic pharmacy. There was no language restriction; searches were executed from onset until June 11, 2020. In addition, experts were invited to suggest relevant literature. Results: Eighty-seven of 660 identified publications were included. The system of anthroposophic medicine (AM) with its conceptual background and various aspects of AMPs was described: definition, pharmaceutical properties, an example of AMP development, use in clinical practice, similarities with and differences to conventional medicinal products, societal aspects, scientific and regulatory assessment. Conclusion: AMPs are part of the integrative whole medical system of AM. AMPs are manufactured according to Good Manufacturing Practice and national drug regulations and have an excellent safety status; the limited available evidence suggests clinical benefits. Current drug regulation of AMPs in the EU and most European countries does not take the special properties of AMPs into account. Future research should focus on appropriate methodologies for the evaluation of effects of AMPs as part of the AM whole medical system, the scientific quality of its non-atomistic holistic ontological position, and the integration of AM and conventional medicine in clinical practice. Future policies should focus on appropriate ways of addressing regulatory challenges to AMPs.

Splenic Rhythms and Postprandial Dynamics in Physiology, Portal Hypertension, and Functional Hyposplenism: A Review.

BACKGROUND: Before the discovery of immunological and haematological functions of the spleen, it had for centuries been considered to be a digestive organ of variable size with a role in the portal vein system and nutritional metabolism. In the 19th and 20th centuries, volume changes in the spleen related to nutrition were studied using plethysmographic measurements. Rhythmical and regulatory functions of the spleen were demonstrated in the haemodynamics of the splanchnic region and were described as a "hepatolienal pendulum," a "Windkessel function," or a "pressure compensation." These studies were mainly published in German-speaking countries and have not, as far as is known, been discussed in the English-speaking world so far. SUMMARY: This review explores the historical development of the rhythmical regulatory function of the spleen in the splanchnic region. Older studies and results are followed up in the modern literature, wherever possible, up to the present. The clinical relevance is illustrated with portal hypertension (with congestive or hyperdynamic splenomegaly), coeliac disease, and chronic inflammatory bowel diseases (with functional hyposplenism). Key Message: The spleen's rhythmical regulatory function in nutrition is based on an autonomous rhythm comprising cycles of contractions and dilations of the spleen of around 1 min. These cycles can be influenced by sympathetically mediated single contractions with a release of pooled blood or by portal vein congestion. After food ingestion, the spleen responds either with contraction according to a vasomotor reaction or postprandial congestion with significant increases in volume. The spleen's rhythmical function is lost in the clinical picture of portal hypertension or in coeliac disease and chronic inflammatory bowel diseases. In the aforementioned gastrointestinal diseases, we recommend taking more account of the haemodynamics between the spleen, liver, and intestine. New innovative techniques for recording splenograms are required which, besides elastographic measurements of spleen stiffness, could offer an important tool for early detection, diagnosis, and therapeutic evaluation.

Binary symbolic dynamics analysis to detect stress-associated changes of nonstationary heart rate variability.

Psychological stress may have harmful physiological effects and result in deteriorating health. Acute psychological stress acts also on cardiac autonomic regulation and may lead to nonstationarities in the interbeat interval series. We address the requirement of stationary RR interval series to calculate frequency domain parameters of heart rate variability (HRV) and use binary symbolic dynamics derived from RR interval differences to overcome this obstacle. 24 healthy subjects (12 female, 20-35 years) completed the following procedure: waiting period, Trier Social Stress Test to induce acute psychological stress, recovery period. An electrocardiogram was recorded throughout the procedure and HRV parameters were calculated for nine 5-min periods. Nonstationarities in RR interval series were present in all periods. During acute stress the average RR interval and SDNN decreased compared to rest before and after the stress test. Neither low frequency oscillations (LF), high frequency oscillations (HF) nor LF/HF could unambiguously reflect changes during acute stress in comparison to rest. Pattern categories derived from binary symbolic dynamics clearly identified acute stress and accompanying alterations of cardiac autonomic regulation. Methods based on RR interval differences like binary symbolic dynamics should be preferred to overcome issues related to nonstationarities.

Does the Spleen Have a Function in Digestion? Medical History, Phylogenetic and Embryological Development of the Splenogastric System.

BACKGROUND: Before the spleen was discovered to be a lymphatic blood organ, it had for centuries been considered to be a digestive organ. Concepts of a regulative, secretory and resorptive function in the digestive system were based mainly on a postulated connection between the stomach and the spleen. Splenogastric vascular connections have recently been rediscovered by modern surgery. SUMMARY: To test the hypothesis that the spleen has a digestive function, this article reviews the literature focusing on the interaction between the spleen and the stomach. We examine the historical medical view of the spleen and stomach system and the reasons why a digestive function was abandoned in the 17th and 18th centuries. We then review the rediscovery of the splenogastric system and the present-day state of knowledge (anatomical origin, variability, haemodynamics) and present it in terms of the phylogenetic and embryological development of the spleen and stomach system. Key Message: Splenogastric arteries and gastrosplenic veins form a portal system which directly connects the spleen and stomach parenchyma. Despite its mesodermal anlage, phylogenetically and embryologically the spleen is intimately interconnected with the entodermal stomach parenchyma but detaches from this in the course of development. Further study is required to establish whether the splenogastric system is merely an evolutive remnant or actually a part of a functioning spleen-stomach system as postulated in complementary and integrative medicine.

Postprandial dynamics of splenic volume in healthy volunteers.

Throughout the history of medicine, many functions have been attributed to the spleen and numerous researchers have focused on a postulated digestive function. Beginning in 1825, systematic animal studies showed evidence for a postprandial increase in splenic volume (SV) with a peak 30 min to five hours after food intake. Since the introduction of imaging techniques, two studies have been conducted on humans, revealing a decrease in SV 30 to 45 min postprandially. The aim of this study was to examine possible postprandial changes in SV over a period of seven hours. The ethics-approved, randomized crossover study included 10 healthy volunteers, who received a standardized meal (3,600 kJ) on one study day and fasted on the other. Sonographic measurements were obtained at six measurement points on each day. Thirty minutes after the meal, SV increased significantly by 38.2 ± 51.2 cm3 (17.3%; p = .04) compared to the baseline measurement and decreased gradually afterward. In males, SV 30 min after the meal was 70.2 ± 21.6 cm3 higher (p = .002) compared to the fasting condition and 60 min later it was still significantly increased. The apparent SV increase after food intake is discussed in relation to hemodynamic changes in the splanchnic region. It seems plausible that the spleen has a rhythmic and regulative function within the portal system, something which warrants further research and should be taken more into account in nutritional physiology.

Development of a whole plant bioassay to test effects of potentized calcium carbonate in pillule formulation.

OBJECTIVES: From a pharmaceutical point of view, we see a need to develop stable preclinical test systems to identify and investigate effects of potentized remedies as used in Anthroposophic Medicine and Homeopathy. We evaluated a plant bioassay regarding its capacity to distinguish homeopathic remedies from placebo, applied as sucrose pillules. METHODS: Pea seed (Pisum sativum L) was soaked for 24 hours in water with dissolved homeopathic or placebo pillules, or in water only. Shoot length was measured 14 days after planting and treatment groups were compared by analysis of variance (ANOVA). The stability of the system was validated by systematic negative control experiments. RESULTS: The system is suitable to test a common application form - sucrose pillules - of a potentized preparation without influence of the pharmaceutical carrier substance. A screening of 13 potentized preparations revealed Calcium carbonicum to affect pea shoot growth (p < 0.05). Three independent series of main experiments were performed with potentized Calcium carbonicum to assess reproducibility. Meta-analysis of all data revealed significant effects of Calcium carbonicum 12c and 30c on pea shoot growth (p < 0.05), which were however dependent on the date of experiment and/or the experimental series. CONCLUSIONS: Potentized Calcium carbonicum, applied as sucrose pillules, influenced pea shoot growth in the assay investigated. However, due to the small effect size and due to the modulation of the effects by still unknown external factors, further optimization of this bioassay is necessary to be used in pharmaceutical quality control or in investigating the biological or pharmaceutical mode of action of potentized preparations.

An assessment of the scientific status of anthroposophic medicine, applying criteria from the philosophy of science.

OBJECTIVES: The objective was to evaluate the scientific status of anthroposophic medicine (AM) according to demarcation criteria proposed in contemporary philosophy of science. DESIGN: Criteria for what is science were retrieved from eight publications in the philosophy of science, focusing either on science in medicine or on the demarcation between science and pseudoscience or non-science. Criteria were combined, redundancies were excluded, and the final set of criteria was ordered in a logical sequence. The analysis yielded 11 demarcation criteria (community, domain, problems, goals, axiomatic basis, conceptual basis, quality of concepts, methodology, deontic basis, research products, tradition). RESULTS: Assessing the scientific status of AM according to the 11 criteria, all criteria were fulfilled by AM. DISCUSSION: AM is grounded on the notion that specific non-atomistic holistic formative forces exist and can be empirically and rationally assessed. From a position claiming that such holistic forces cannot possibly exist or cannot be empirically and rationally assessed, the axiomatic and conceptual basis of AM can be contested. However, such an a priori rejection is problematic in the presence of empirical evidence supporting the validity of holistic concepts, as discussed in the paper. Future research should therefore focus on the tenability of the ontological reductionist position in science and on the further validation of AM non-atomistic holistic concepts, methods and practices. CONCLUSION: In this analysis, using criteria from philosophy of science, AM fulfilled all 11 criteria for what is science.

Stress-associated changes in salivary microRNAs can be detected in response to the Trier Social Stress Test: An exploratory study.

Stress is an important co-factor for the genesis and maintenance of many diseases and is known to have an effect on gene expression via epigenetic regulation. MicroRNAs (miRNAs) appear to function as one of the key factors of this regulation. This is the first study to investigate the response of 11 stress-associated miRNAs in human saliva - as a non-invasive source - in an experimental condition of acute psychological stress, and also their correlation with established psychological (subjective stress perception), physiological (heart rate and heart rate variability) and biochemical stress parameters (salivary cortisol and alpha-amylase). 24 healthy participants between 20 and 35 years of age were investigated, using the Trier Social Stress Test (TSST) to induce acute psychological stress. Stress-associated changes were significant for miR-20b, -21 and 26b, and changes in miR-16 and -134 were close to significance, recommending further research on these miRNAs in the context of stress reactions. Significant correlations with alpha-amylase suggest their integration in sympathetic stress regulation processes. Additionally, our results demonstrate the TSST as a reliable tool for studying salivary miRNAs as non-invasive indicators of epigenetic processes in acute psychological stress reactions.

Can Speech-Guided Breathing Influence Cardiovascular Regulation and Mood Perception in Hypertensive Patients?

OBJECTIVES: Anthroposophic therapeutic speech (ATS) has been shown to positively influence heart rate variability (HRV) and cardiorespiratory coordination in healthy volunteers. This prospective, exploratory, pre-post study was performed to investigate ATS effects on baroreflex sensitivity (BRS), heart rate (HR), HRV by standard deviation of beat to beat intervals (SDNN), blood pressure (BP), and mood in hypertensive patients. DESIGN: Patients received three ATS treatments, alternating with three sham interventions (control). During the sessions, BP and electrocardiography were continuously recorded. BRS and SDNN were analyzed from those measurements. Changes in mood score were assessed by a questionnaire. All data were compared before and after intervention (ATS and control). RESULTS: Thirty-one patients participated, the majority diagnosed with arterial hypertension (22 out of 31). Pre-post analysis of the data revealed immediate and significant changes in hypertensive patients during control and ATS with respect to BRS (control: 6.57 to 6.92 msec/mmHg, p = 0.0349; ATS: 6.03 to 7.27 msec/mmHg, p < 0.0001), SDNN (control: 39 to 42 msec, p = 0.0058; ATS: 38 to 43 msec, p = 0.0003), and HR (control: 74 to 71 beats per minute [bpm], p < 0.0001; ATS: 74 to 70 bpm, p < 0.0001). In normotensive patients, those changes were generally less pronounced and less significant with respect to BRS (control: 8.13 to 8.56 msec/mmHg, p = 0.1102; ATS: 8.20 to 8.98 msec/mmHg, p = 0.0273), SDNN (control: 36 to 40 msec, p = 0.0002; ATS: 35 to 38 msec, p = 0.0556), and HR (control: 80 to 77 bpm, p < 0.0001; ATS: 80 to 78 bpm, p < 0.0011). Only in hypertensive patients significant long-term changes were observed for BRS (6.6 to 7.7 msec/mmHg, p = 0.0070), SDNN (39.1 to 45.5 msec, p = 0.0074), and HR (75.8 to 67.2 bpm, p = 0.0001). No significant long-term changes were observed in normotensive patients. The mean systolic BP did not change significantly during this study. Both ATS and control also yielded improvements in the mood summary score, which again were more apparent for ATS than for sham interventions, but these were more pronounced among normotensive patients (3.5 to 4.2) than for hypertensive patients (2.9 to 3.9). CONCLUSION: The results indicate that ATS has the potential to improve cardiovascular parameters which play an important role in BP regulation capability.

Design of a Self-Management Program for Children Aged 6-12 Years with Type 1 Diabetes Mellitus at the Community Hospital Herdecke, Germany.

BACKGROUND: Children with type 1 diabetes mellitus (T1DM) must replace lacking endogenous insulin by daily insulin injections or insulin pumps. Standards of treatment include educational programs enabling self-management. The program 'Herdecker Kids with Diabetes' (HeKiDi) is based on an anthroposophic understanding of the human being and intends to provide an individualized, patient-oriented approach to developing diabetes-related and comprehensive human competencies. AIM: Analysis of the HeKiDi program for children (6-12 years) with T1DM as the first part of an evaluation of a complex intervention. METHODS: Ethnographic approach, following the Consolidated Criteria for Reporting Qualitative Research (COREQ), including field observations and interviews with responsible persons, content analysis of materials for determining the structure and the curriculum, presented according to the Template for Intervention Description and Replication (TIDieR). RESULTS: The curriculum follows the standard but adds a learning circle between the child and the therapeutic team comprising 3 stages: (1) perception of the abilities and needs of the individual child supported by adult mentors themselves suffering from T1DM, (2) reflection within the therapeutic team, and (3) daily feedback to the child. Curricular Learning Objectives: Children feel recognized and supported in their individual developmental and diabetes-related competencies and develop motoric, artistic, communicative, and social skills to strengthen their self-efficacy and to understand T1DM as a lifelong awareness process. CONCLUSIONS: The curriculum including its associated learning goals and methods was presented. The program was explained and shown to be reproducible. Whether this program truly leads to better outcomes in regard to self-efficacy and hemoglobin A1c (HbA1c, glycated hemoglobin) and how parents and children perceive this will have to be assessed using a comparative interventional study.

Does the model of additive effect in placebo research still hold true? A narrative review.

Personalised and contextualised care has been turned into a major demand by people involved in healthcare suggesting to move toward person-centred medicine. The assessment of person-centred medicine can be most effectively achieved if treatments are investigated using 'with versus without' person-centredness or integrative study designs. However, this assumes that the components of an integrative or person-centred intervention have an additive relationship to produce the total effect. Beecher's model of additivity assumes an additive relation between placebo and drug effects and is thus presenting an arithmetic summation. So far, no review has been carried out assessing the validity of the additive model, which is to be questioned and more closely investigated in this review. Initial searches for primary studies were undertaken in July 2016 using Pubmed and Google Scholar. In order to find matching publications of similar magnitude for the comparison part of this review, corresponding matches for all included reviews were sought. A total of 22 reviews and 3 clinical and experimental studies fulfilled the inclusion criteria. The results pointed to the following factors actively questioning the additive model: interactions of various effects, trial design, conditioning, context effects and factors, neurobiological factors, mechanism of action, statistical factors, intervention-specific factors (alcohol, caffeine), side-effects and type of intervention. All but one of the closely assessed publications was questioning the additive model. A closer examination of study design is necessary. An attempt in a more systematic approach geared towards solutions could be a suggestion for future research in this field.

MicroRNAs in Psychological Stress Reactions and Their Use as Stress-Associated Biomarkers, Especially in Human Saliva.

MicroRNAs (miRNAs) play a central role in the regulation of many cellular processes including physiological and psychological stress reaction pathways. Psychological stress is an important factor for the genesis and maintenance of many diseases. Several miRNAs have already been described to be involved in its regulation. The presence of miRNAs in all body fluids implies a widespread role in communication throughout the whole organism and together with their stability makes them formidable candidates as biomarkers. Alterations of stress-associated miRNA expression levels have been found in the brain and whole blood of humans and animals. In this paper, we review the participation of miRNAs in stress-reactive processes as well as their usability as salivary biomarkers of such processes. In conclusion, we suggest that salivary miRNAs may be useful as noninvasive biomarkers to assess epigenetic regulation processes of chronic or acute psychological stress reactions.

Mistletoe Berry Outline Mapping with a Path Curve Function and Recording the Circadian Rhythm of Their Phenotypic Shape Change.

This paper presents a discovery: the change of the outline shape of mistletoe (Viscum album ssp. album) berries in vivo and in situ during ripening. It was found that a plant organ that is usually considered to merely increase in size actually changes shape in a specific rhythmic fashion. We introduce a new approach to chronobiological research on a macro-phenotypic scale to trace changes over long periods of time (with a resolution from hours to months) by using a dynamic form-determining parameter called Lambda (λ). λ is known in projective geometry as a measure for pertinent features of the outline shapes of egg-like forms, so called path curves. Ascertained circadian changes of form were analyzed for their correlation with environmental factors such as light, temperature, and other weather influences. Certain weather conditions such as sky cover, i.e., sunshine minutes per hour, have an impact on the amplitude of the daily change in form. The present paper suggests a possible supplement to established methods in chronobiology, as in this case the dynamic of form-change becomes a measurable feature, displaying a convincing accordance between mathematical rule and plant shape.

Women's perceptions of induction of labour outcomes: Results of an online-survey in Germany.

OBJECTIVE: induction of labour (IOL) is a common procedure in high income countries. It may be conducted for medical as well as non-medical reasons. Women's views on induction of labour have not extensively been evaluated as yet. Also, women's preferences for certain methods of induction including alternative and complementary methods need further exploration in order to meet their expectations and needs. DESIGN AND SETTING: we published a short online questionnaire on women'views and experiences with IOL. MEASUREMENTS AND FINDINGS: we asked for indication and gestational age at induction; method of induction, duration of labour and mode of birth. We also asked for the extent of desired, and experienced support and participation in decision-making. Within four weeks of being online, 698 women answered the questionnaire. Most frequent reasons for induction were postmaturity (51.7%), doctor's recommendation (31.6%) and medical complications (25.6%). Most women were induced with misoprostol or dinoprostone, but nearly half of the respondents were also offered, or asked for, complementary and alternative methods (CAM). 50% or more women would have preferred more information on alternatives to IOL, methods of IOL, side effects of the drugs, information on alternatives (59.2%) and on the medication (55.3%). Many would have wished for more support (49.9%) with decision-making (55.2%), and more time (54.1%). KEY CONCLUSION: women' expectations and needs regarding IOL are widely unmet in current clinical practice. IMPLICATIONS FOR PRACTICE: there is a need for evidence-based information and decisional support for pregnant women who need to decide how to proceed once term is reached.

Temporal trends in fetal mortality at and beyond term and induction of labor in Germany 2005-2012: data from German routine perinatal monitoring.

PURPOSE: While a variety of factors may play a role in fetal and neonatal deaths, postmaturity as a cause of stillbirth remains a topic of debate. It still is unclear, whether induction of labor at a particular gestational age may prevent fetal deaths. METHODS: A multidisciplinary working group was granted access to the most recent set of relevant German routine perinatal data, comprising all 5,291,011 hospital births from 2005 to 2012. We analyzed correlations in rates of induction of labor (IOL), perinatal mortality (in particular stillbirths) at different gestational ages, and fetal morbidity. Correlations were tested with Pearson's product-moment analysis (α = 5 %). All computations were performed with SPSS version 22. RESULTS: Induction rates rose significantly from 16.5 to 21.9 % (r = 0.98; p < 0.001). There were no significant changes in stillbirth rates (0.28-0.35 per 100 births; r = 0.045; p = 0.806). Stillbirth rates 2009-2012 remained stable in all gestational age groups irrespective of induction. Fetal morbidity (one or more ICD-10 codes) rose significantly during 2005-2012. This was true for both children with (from 33 to 37 %, r = 0.784, p < 0.001) and without (from 25 to 31 %, (r = 0.920, p < 0.001) IOL. CONCLUSIONS: An increase in IOL at term is not associated with a decline in perinatal mortality. Perinatal morbidity increased with and without induction of labor.

Placebo effects in medicine: A bibliometric analysis.

OBJECTIVE: It was the aim of this bibliometric analysis to identify all publications dealing with so-called 'context effects/placebo effects' to bring some organisation into the publication landscape of the past 35 years. DESIGN: An electronic database search was carried out in Pubmed from its inception to November 2011. PARTICIPANTS: Already published articles and their participants were included. SETTING: This review was carried out at an academic institution. MAIN OUTCOME MEASURES: Condition, country, year, journal, number of authors, type of publication and main focus of the publication. RESULTS: There are slight differences in the focus and the origin of research. Although the subject is multidimensional and covering all areas in healthcare, only a few research disciplines cover the field of placebo effects. The research field is shrinking as evident by the smaller number of researchers publishing in this field. It is suggested that the discussion regarding placebo and context effects is getting more homogenous and is turning into a specific field by itself. There is an increasing concentration of placebo effects being reproduced in experimental settings. CONCLUSION: It is debatable whether the complexity of the broad range of what produces placebo effects can be successfully detected in a randomized controlled trial setting.

Watchful waiting or induction of labour--a matter of informed choice: identification, analysis and critical appraisal of decision aids and patient information regarding care options for women with uncomplicated singleton late and post term pregnancies: a review.

BACKGROUND: Decision-making during pregnancy regarding different options of care can be difficult, particularly when risks of intervention versus no intervention for mother and baby are unclear. Unbiased information and support for decision making may be beneficial in these situations. The management of normal pregnancies at and beyond term is an example of such a situation. In order to determine the need to develop an evidence-based decision aid this paper searches, analyses and appraises patient decision aids and patient information leaflets regarding care options in cases of late term and post-term pregnancies, including complementary and alternative medicine (CAM). METHODS: A literature search was carried out in a variety of lay and medical databases. INCLUSION CRITERIA: written information related to uncomplicated singleton pregnancies and targeted at lay people. Analysis and appraisal of included material by means of quality criteria was set up based on the International Patient Decision Aid Standards accounting for evidence-basing of CAM options. RESULTS: Inclusion of two decision aids and eleven leaflets from four decision aids and sixteen leaflets. One decision aid met the quality criteria almost completely, the other one only insufficiently despite providing some helpful information. Only one leaflet is of good quality, but cannot substitute a decision aid. CONCLUSIONS: There is an urgent need for the design of an evidence-based decision aid of good quality for late-term or post-term pregnancy, particularly in German language.

Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro.

BACKGROUND: Macrophages are highly versatile cells that play an important role in tumour microenvironment. Tumour associated macrophages (TAMs) have been linked to both, good or bad prognosis of several cancer types depending on their number, composition and polarization. Viscum album lipophilic extract (VALE) contains several pentacyclic triterpenes known to modulate the activity of monocytes and other immune cells and to exhibit anticancer properties. In our in vitro study, we investigated the effect of tumour cell lines on macrophage polarization and monocyte chemotactic transmigration and examined the modulatory potential of VALE and its predominant triterpene oleanolic acid (OA). METHODS: Human peripheral blood monocytes were differentiated into monocyte derived macrophages (MDM) using M-CSF and polarized into M1 by IFN-γ and LPS and into M2 macrophages by IL-4 and IL-13 or by co-culture with two different tumour cell lines. Polarized macrophages were subsequently treated with VALE or OA. Phenotypic markers and cytokines were assessed by flow cytometry and immunoanalysis. Migration of human peripheral blood monocytes induced by monocyte chemotactic protein-1 (MCP-1) or supernatants of different tumour cell lines under the influence of VALE or OA was measured in a chemotaxis transmigration assay. RESULTS: In vitro polarized M1 and M2 type macrophages revealed specific phenotypic patterns and tumour cell co-cultured MDM displayed ambiguous phenotypes with M1 as well as M2 associated markers. VALE and OA showed modest influence on cell surface marker profile and cytokine expression of tumour cell co-cultured macrophages. All tumour cell supernatants markedly enhanced the migratory activity of monocytes. VALE and OA significantly inhibited MCP-1 induced monocyte transmigration, whereas monocyte migration initiated by tumour cell derived supernatants was not affected. CONCLUSIONS: In our study we reconfirmed that co-culture with different tumour cell lines can result in a mixed macrophage phenotype with M1 as well as M2 patterns, a finding that is important for a better understanding of tumour microenvironment functions. Moreover, we demonstrated that VALE shows slight immunomodulatory effects on tumour cell co-cultured macrophages and modulates monocyte chemotactic transmigration in vitro, indicating promising possibilities of triterpenes from Viscum album L. to contribute in a multimodal concept of anti-cancer therapy in future. Our data contribute to an understanding of monocyte function and macrophage polarization in vitro and of the possibility to influence their behaviour by triterpene containing mistletoe extracts.